载脂蛋白M可能经NF-κB介导大鼠肾缺血再灌注损伤

Apolipoprotein M mediates renal ischemia reperfusion injury probably via NF-κB in rats

目的观察核因子-кB抑制剂——吡咯烷二硫代氨基甲酸盐(PDTC)对缺血再灌注(IRI)大鼠肾组织载脂蛋白M(APOM)表达的影响,探讨APOM参与肾IRI发病的机制。方法 75只雄性SD大鼠分为假手术(sham)组、IRI组和PDTC组。用real time PCR和Western blot法,检测不同时间点肾皮质APOM和核内NF-кB P65的表达。结果 IRI组各时间点核内NF-кB P65水平均较sham组明显增高(sham组1.0±0.2;IRI3h组4.1±0.5,P<0.01),PDTC组表达明显低于IRI组(PDTC3h组2.0±0.2,P<0.01),并呈双峰样改变,表达高峰分别在再灌注3和48 h。APOM mRNA水平在IRI组各时间点也较sham组明显增高(sham组0.9±0.1;IRI3h组6.6±2.3,P<0.01),PDTC组的表达较IRI组降低(PDTC3h组3.3±0.8,P<0.01),也呈双峰型表达趋势,表达高峰分别在再灌注3和48 h;APOM蛋白的表达模式与mRNA相同,但表达高峰较mRNA滞后。APOM mRNA与核内NF-кB P65的表达呈明显正相关。结论 APOM可能通过NF-кB介导肾IRI的发病。

Objective To investigate the effect of NF-κB inhibitor-pyrrolidine dithiocarbamat（PDTC） on the expression of APOM in renal cortex of rats with ischemia reperfusion injury（IRI）.Methods Seventy-five male rats were randomly divided into sham operation group、IRI group and PDTC group,five subgroups at time points of 3,6,12,24 and 48 h after reperfusion were set up in each group.The expression of mRNA and protein of APOM in cytoplasm and that of NF-κB P65 protein in nucleus of renal cortex were detected at the indicated time points.ResultsThe expression of NF-кB P65 protein in IRI group was obviously higher than that in sham operation group（sham：1.0±0.2;IRI3h：4.1±0.5,P0.01）,while the expression in PDTC group was lower than that in IRI group（PDTC3h：2.0±0.2,P0.01）,and two peaks were detected,which were respectively at 3 and 48 h after reperfusion.A similar expression pattern of both mRNA and protein of APOM was found among the three groups,and there were also two peaks in expression of APOM,the expression peaks of APOM mRNA was at 3 and 48 h after reperfusion,while those of APOM protein lag behind.Otherwise,a significant correlation was found between the expression of APOM mRNA and NF-κB P65.Conclusions APOM feasibly takes part in the pathogenesis of IRI via NF-кB.